Injection of F1 hybrid mice with either murine cytomegalovirus (MCMV) or parental spleen cells (graft-versus-host reaction - GVHR) results in rapid and severe immunosuppression. Inoculation of either the virus or parental cells were selected so that they would be below the threshold for severe immunosuppression. However, when these two inocula were combined, severe immunosuppression was observed. Furthermore, injection of F1 mice with parental lymphocytes that recognize only class I MHC determinants does not result in immune suppression. However, a combination of class I recognition and MCMV infection results in profound immune suppression. In contrast, there was no detectable synergy between class II GVH and MCMV. Infection of mice with MCMV was found to elevate natural killer (NK) cell number and activity. As a consequence MCMV infection was able to augment natural resistance and the rejection of bone marrow grafts.